{"title":"Oxygen diffusion pathways in mutated forms of a LOV photoreceptor from <i>Methylobacterium radiotolerans</i>: A molecular dynamics study.","authors":"Rocco Zerlotti, Aba Losi, Eugenia Polverini","doi":"10.1515/bmc-2022-0013","DOIUrl":"https://doi.org/10.1515/bmc-2022-0013","url":null,"abstract":"<p><p><i>Mr</i>4511 from <i>Methylobacterium radiotolerans</i> is a photoreceptor of the light, oxygen voltage (LOV) family, binding flavin mononucleotide (FMN) as a chromophore. It exhibits the prototypical LOV photocycle, with the reversible formation of an FMN-Cys71 adduct via fast decay of the FMN triplet state. <i>Mr</i>4511 has high potential as a photosensitiser for singlet oxygen (SO) upon mutation of C71. <i>Mr</i>4511-C71S shows a triplet lifetime (<i>τ</i> <sub>T</sub>) of several hundreds of microseconds, ensuring efficient energy transfer to dioxygen to form SO. In this work, we have explored the potential diffusion pathways for dioxygen within <i>Mr</i>4511 using molecular dynamics (MD) simulations. The structural model of wild-type (wt) <i>Mr</i>4511 showed a dimeric structure stabilised by a strong leucine zipper at the two C-terminal helical ends. We then introduced <i>in silico</i> the C71S mutation and analysed transient and persistent oxygen channels. MD simulations indicate that the chromophore binding site is highly accessible to dioxygen. Mutations that might favour SO generation were designed based on their position with respect to FMN and the oxygen channels. In particular, the C71S-Y61T and C71S-Y61S variants showed an increased diffusion and persistence of oxygen molecules inside the binding cavity.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"164-174"},"PeriodicalIF":0.0,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40328291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Calcium signaling in prostate cancer cells of increasing malignancy.","authors":"Carla Marchetti","doi":"10.1515/bmc-2022-0012","DOIUrl":"https://doi.org/10.1515/bmc-2022-0012","url":null,"abstract":"<p><p>Calcium signaling controls a large variety of cell functions, including proliferation and apoptosis, and plays a major role in neoplastic transformation. Prostate cancer (PCa) is one of the most common malignancies in men. The transition to castration-resistant prostate cancer (CRPC), a lethal form that is still lacking an effective cure, could be influenced by fine tuning intracellular calcium ([Ca<sup>2+</sup>]<sub>i</sub>) homeostasis. This study investigates [Ca<sup>2+</sup>]<sub>i</sub> dynamics in metastatic PCa cell lines that mimic the progression of PCa to CRPC: (i) well differentiated LNCaP cells that require androgen for survival, and (ii) poorly differentiated, highly aggressive androgen-insensitive prostate cancer (AIPC) PC3 and DU145 cells. In AIPC cells, ATP induces a fast rise in [Ca<sup>2+</sup>]<sub>i</sub>, due to release from intracellular stores and sensitive to phospholipase C inhibitors, while LNCaP cells do not respond to ATP challenge. Moreover, AIPC cells showed a reduced capacity to store Ca<sup>2+</sup> in thapsigargin-sensitive stores and limited store-operated calcium entry, with respect to androgen-dependent LNCaP cells. Finally, green tea extract causes [Ca<sup>2+</sup>]<sub>i</sub> elevation and inhibits proliferation in PC3 and DU145 cells, but is ineffective in LNCaP cells. The consequences of these differences are discussed and interpreted in this study with reference to previously proposed models for Ca<sup>2+</sup> dependence of prostate carcinogenesis.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"156-163"},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40327339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miriam Grava, Sally Helmy, Mario Gimona, Pietro Parisse, Loredana Casalis, Paola Brocca, Valeria Rondelli
{"title":"Calorimetry of extracellular vesicles fusion to single phospholipid membrane.","authors":"Miriam Grava, Sally Helmy, Mario Gimona, Pietro Parisse, Loredana Casalis, Paola Brocca, Valeria Rondelli","doi":"10.1515/bmc-2022-0011","DOIUrl":"https://doi.org/10.1515/bmc-2022-0011","url":null,"abstract":"<p><p>Extracellular vesicles (EVs)-mediated communication relies not only on the delivery of complex molecular cargoes as lipids, proteins, genetic material, and metabolites to their target cells but also on the modification of the cell surface local properties induced by the eventual fusion of EVs' membranes with the cells' plasma membrane. Here we applied scanning calorimetry to study the phase transition of single phospholipid (DMPC) monolamellar vesicles, investigating the thermodynamical effects caused by the fusion of doping amounts of mesenchymal stem cells-derived EVs. Specifically, we studied EVs-induced consequences on the lipids distributed in the differently curved membrane leaflets, having different density and order. The effect of EV components was found to be not homogeneous in the two leaflets, the inner (more disordered one) being mainly affected. Fusion resulted in phospholipid membrane flattening associated with lipid ordering, while the transition cooperativity, linked to membrane domains' coexistence during the transition process, was decreased. Our results open new horizons for the investigation of the peculiar effects of EVs of different origins on target cell membrane properties and functionality.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"148-155"},"PeriodicalIF":0.0,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40308019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roksana Bobrowska, Aleksandra Noweiska, Julia Spychała, Agnieszka Tomkowiak, Jerzy Nawracała, Michał T Kwiatek
{"title":"Diagnostic accuracy of genetic markers for identification of the <i>Lr46/Yr29</i> \"slow rusting\" locus in wheat (<i>Triticum aestivum</i> L.).","authors":"Roksana Bobrowska, Aleksandra Noweiska, Julia Spychała, Agnieszka Tomkowiak, Jerzy Nawracała, Michał T Kwiatek","doi":"10.1515/bmc-2022-0002","DOIUrl":"https://doi.org/10.1515/bmc-2022-0002","url":null,"abstract":"<p><p>Wheat leaf rust, caused by fungal pathogen <i>Puccinia triticina</i> Erikss, annually contributes to production losses as high as 40% in susceptible varieties and remains as one of the most damaging diseases of wheat worldwide. Currently, one of the major challenges of wheat geneticists and breeders is to accumulate major genes for durability of rust resistance called \"slow rusting\" genes using marker-assisted selection (MAS). Until now, eight genes (<i>Lr34/Yr18</i>, <i>Lr46/Yr29</i>, <i>Lr67/Yr46</i>, <i>Lr68</i>, <i>Lr74</i>, <i>Lr75</i>, <i>Lr77</i>, and <i>Lr78</i>) conferring resistance against multiple fungal pathogens have been identified in wheat gene pool and the molecular markers were developed for them. In MAS practice, it is a common problem that cultivars exhibiting desirable marker genotypes may not necessarily have the targeted genes or alleles and vice versa, which is known as \"false positives.\" The aim of this study was to compare the available four markers: <i>Xwmc44</i>, <i>Xgwm259</i>, <i>Xbarc80</i>, and <i>csLV46G22</i> markers (not published yet), for the identification of the <i>Lr46/Yr29</i> loci in 73 genotypes of wheat, which were reported as sources of various \"slow rusting\" genes, including 60 with confirmed <i>Lr46/Yr29</i> gene, reported in the literature. This research revealed that <i>csLV46G22</i> together with <i>Xwmc44</i> is most suitable for the identification of resistance allele of the <i>Lr46/Yr29</i> gene; however, there is a need to clone the <i>Lr46/Yr29</i> loci to identify and verify the allelic variation of the gene and the function.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2022-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39960200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of omega-3 fatty acids on the telomere length: A mini meta-analysis of clinical trials.","authors":"Sawan Ali, Giovanni Scapagnini, Sergio Davinelli","doi":"10.1515/bmc-2021-0024","DOIUrl":"https://doi.org/10.1515/bmc-2021-0024","url":null,"abstract":"<p><p>Telomeres are protective caps at the end of eukaryotic chromosomes, whose length is correlated with health and lifespan. Telomere attrition is a common feature of the aging process and can be accelerated by oxidative stress and chronic inflammation. Various nutrients influence the telomere length, partially due to their antioxidant and anti-inflammatory properties. The aim of this review was to meta-analytically assess the effect of omega-3 fatty acids on the telomere length. We searched four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) from inception until November 2021. Of 573 records, a total of 5 clinical trials were included for the quantitative meta-analysis, comprising a total of 337 participants. The results revealed an overall beneficial effect of omega-3 fatty acids on the telomere length (mean difference = 0.16; 95% CI, 0.02, 0.30; <i>p</i> = 0.02). Despite a limited number of studies, the available evidence suggests that omega-3 fatty acids may positively affect the telomere length. However, larger clinical trials are needed to confirm our findings, along with studies aimed to clarify the underlying molecular mechanisms.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"25-33"},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39942342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of differentially expressed genes and signaling pathways involved in atherosclerosis and chronic obstructive pulmonary disease.","authors":"Stanislav Kotlyarov","doi":"10.1515/bmc-2022-0001","DOIUrl":"https://doi.org/10.1515/bmc-2022-0001","url":null,"abstract":"<p><p>Atherosclerosis is an important medical and social problem, and the keys to solving this problem are still largely unknown. A common situation in real clinical practice is the comorbid course of atherosclerosis with chronic obstructive pulmonary disease (COPD). Diseases share some common risk factors and may be closely linked pathogenetically.</p><p><strong>Methods: </strong>Bioinformatics analysis of datasets from Gene Expression Omnibus (GEO) was performed to examine the gene ontology (GO) of common differentially expressed genes (DEGs) in COPD and peripheral arterial atherosclerosis. DEGs were identified using the limma R package with the settings <i>p</i> < 0.05, corrected using the Benjamini & Hochberg algorithm and ǀlog 2FCǀ > 1.0. The GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and the protein-protein interaction (PPI) network analysis were performed with the detected DEGs.</p><p><strong>Results: </strong>The biological processes and signaling pathways involving common DEGs from airway epithelial datasets in COPD and tissue in peripheral atherosclerosis were identified. A total of 15 DEGs were identified, comprising 12 upregulated and 3 downregulated DEGs. The GO enrichment analysis demonstrated that the upregulated hub genes were mainly involved in the inflammatory response, reactive oxygen species metabolic process, cell adhesion, lipid metabolic process, regulation of angiogenesis, icosanoid biosynthetic process, and cellular response to a chemical stimulus. The KEGG pathway enrichment analysis demonstrated that the common pathways were Toll-like receptor signaling pathway, NF-kappa B signaling pathway, lipid and atherosclerosis, and cytokine-cytokine receptor interaction.</p><p><strong>Conclusions: </strong>Biological processes and signaling pathways associated with the immune response may link the development and progression of COPD and atherosclerosis.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"34-54"},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39942344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Maria Posadino, Gian Luca Erre, Annalisa Cossu, Costanza Emanueli, Ali H Eid, Angelo Zinellu, Gianfranco Pintus, Roberta Giordo
{"title":"NADPH-derived ROS generation drives fibrosis and endothelial-to-mesenchymal transition in systemic sclerosis: Potential cross talk with circulating miRNAs.","authors":"Anna Maria Posadino, Gian Luca Erre, Annalisa Cossu, Costanza Emanueli, Ali H Eid, Angelo Zinellu, Gianfranco Pintus, Roberta Giordo","doi":"10.1515/bmc-2021-0023","DOIUrl":"10.1515/bmc-2021-0023","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is an immune disorder characterized by diffuse fibrosis and vascular abnormalities of the affected organs. Although the etiopathology of this disease is largely unknown, endothelial damage and oxidative stress appear implicated in its initiation and maintenance. Here, we show for the first time that circulating factors present in SSc sera increased reactive oxygen species (ROS) production, collagen synthesis, and proliferation of human pulmonary microvascular endothelial cells (HPMECs). The observed phenomena were also associated with endothelial to mesenchymal transition (EndMT) as indicated by decreased von Willebrand factor (vWF) expression and increased alpha-smooth muscle actin, respectively, an endothelial and mesenchymal marker. SSc-induced fibroproliferative effects were prevented by HPMECs exposition to the NADPH oxidase inhibitor diphenyleneiodonium, demonstrating ROS's causative role and suggesting their cellular origin. Sera from SSc patients showed significant changes in the expression of a set of fibrosis/EndMT-associated microRNAs (miRNA), including miR-21, miR-92a, miR-24, miR-27b, miR-125b, miR-29c, and miR-181b, which resulted significantly upregulated as compared to healthy donors sera. However, miR29b resulted downregulated in SSc sera, whereas no significant differences were found in the expression of miR-29a in the two experimental groups of samples. Taking together our data indicate NADPH oxidase-induced EndMT as a potential mechanism of SSc-associated fibrosis, suggesting fibrosis-associated miRNAs as potentially responsible for initiating and sustaining the vascular alterations observed in this pathological condition.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"11-24"},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9459349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahmoud Soliman Abdel-Hamid, Amr Fouda, Hesham Kamal Abo El-Ela, Abbas A El-Ghamry, Saad El-Din Hassan
{"title":"Erratum to \"Plant growth-promoting properties of bacterial endophytes isolated from roots of <i>Thymus vulgaris</i> L. and investigate their role as biofertilizers to enhance the essential oil contents\".","authors":"Mahmoud Soliman Abdel-Hamid, Amr Fouda, Hesham Kamal Abo El-Ela, Abbas A El-Ghamry, Saad El-Din Hassan","doi":"10.1515/bmc-2021-0025","DOIUrl":"10.1515/bmc-2021-0025","url":null,"abstract":"","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39942343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The epigenetic dimension of protein structure.","authors":"Fodil Azzaz, Jacques Fantini","doi":"10.1515/bmc-2022-0006","DOIUrl":"https://doi.org/10.1515/bmc-2022-0006","url":null,"abstract":"<p><p>Accurate prediction of protein structure is one of the most challenging goals of biology. The most recent achievement is AlphaFold, a machine learning method that has claimed to have solved the structure of almost all human proteins. This technological breakthrough has been compared to the sequencing of the human genome. However, this triumphal statement should be treated with caution, as we identified serious flaws in some AlphaFold models. Disordered regions are often represented by large loops that clash with the overall protein geometry, leading to unrealistic structures, especially for membrane proteins. In fact, AlphaFold comes up against the notion that protein folding is not solely determined by genomic information. We suggest that all parameters controlling the structure of a protein without being strictly encoded in its amino acid sequence should be coined \"epigenetic dimension of protein structure.\" Such parameters include for instance protein solvation by membrane lipids, or the structuration of disordered proteins upon ligand binding, but exclude sequence-encoded sites of post-translational modifications such as glycosylation. In our view, this paradigm is necessary to reconcile two opposite properties of living systems: beyond rigorous biological coding, evolution has given way to a certain level of uncertainty and anarchy.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"55-60"},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39942345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ariyan Manikandan, I. Johnson,, N. Jaivel, R. Krishnamoorthy, M. Senthilkumar, R. Raghu, N. O. Gopal, P. Mukherjee, R. Anandham
{"title":"Gamma-induced mutants of Bacillus and Streptomyces display enhanced antagonistic activities and suppression of the root rot and wilt diseases in pulses","authors":"Ariyan Manikandan, I. Johnson,, N. Jaivel, R. Krishnamoorthy, M. Senthilkumar, R. Raghu, N. O. Gopal, P. Mukherjee, R. Anandham","doi":"10.1515/bmc-2022-0004","DOIUrl":"https://doi.org/10.1515/bmc-2022-0004","url":null,"abstract":"Abstract This study aims to increase Bacillus and Streptomyces antagonistic activity against the root rot and wilt diseases of pulses caused by Macrophomina phaseolina and Fusarium oxysporum f. sp. udum, respectively. To increase antagonistic action, Bacillus subtilis BRBac4, Bacillus siamensis BRBac21, and Streptomyces cavourensis BRAcB10 were subjected to random mutagenesis using varying doses of gamma irradiation (0.5–3.0 kGy). Following the irradiation, 250 bacterial colonies were chosen at random for each antagonistic strain and their effects against pathogens were evaluated in a plate assay. The ERIC, BOX, and random amplified polymorphic studies demonstrated a clear distinction between mutant and wild-type strains. When mutants were compared to wild-type strains, they showed improved plant growth-promoting characteristics and hydrolytic enzyme activity. The disease suppression potential of the selected mutants, B. subtilis BRBac4-M6, B. siamensisi BRBac21-M10, and S. cavourensis BRAcB10-M2, was tested in green gram, black gram, and red gram. The combined inoculation of B. siamensis BRBac21-M10 and S. cavourensis BRAcB10-M2 reduced the incidence of root rot and wilt disease. The same treatment also increased the activity of the defensive enzymes peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase. These findings suggested that gamma-induced mutation can be exploited effectively to improve the biocontrol characteristics of Bacillus and Streptomyces. Following the field testing, a combined bio-formulation of these two bacteria may be utilised to address wilt and root-rot pathogens in pulses.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"103 - 118"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43083875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}